DESCRIPTION: Autonomic neurons in the hypothalamic paraventricular nucleus (PVN) are considered to have a major influence on cardiovascular and body fluid regulatory functions through their dense innervation of the rostral ventrolateral medulla (RVLM), the nucleus tractus solitarius (NTS) and the intermediolateral cell column (IML). In particular, PVN neurons mediate sympathetic responses to both isotonic volume expansion and central osmoreceptor activation. How volume and osmotic afferent signal s are integrated at the level of single PVN neurons is not understood. The proposed experiments will test the hypothesis that neurons projecting to the IML are a primary PVN substrate for the cardiovascular and sympathetic responses to volume expansion and depletion. Neural pathways connecting the PVN to the RVLM, NTS and IML are hypothesized to each play a unique role in the response to central osmotic stimulation. Integrated responses to simultaneous activation of osmotic and volume-sensitive afferents is hypothesized to involve interactions among angiotensinergic and GABAergic inputs. Combining retrograde transport and Fos protein staining will be used to compare the relative degree to which each of these 3 PVN efferent pathways responds to volume depletion and central hyperosmolality. Inactivation studies will be used to determine how each pathway participates in hemorrhage- and hyperosmolality-induced responses. Responses to volume expansion, hemorrhage and central osmotic stimulation will be compared among individual PVN neurons with axonal projections to the RVLM, NTS and the IML. Iontophoretic application of antagonists will be used to determine the role of GABAergic and angiotensinergic neurotransmission in mediating these single unit responses. The results will provide new insight into the role of diverse autonomic pathways arising from the PVN in maintaining volume and osmotic homeostasis.